The care of hepatitis C virus (HCV) in African Americans represents an opportunity to address a major health disparity in medicine. In all facets of HCV infection, African Americans are inexplicably affected, including in the prevalence of the virus, which is higher among them compared with most of the racial and ethnic groups. Ironically, although fibrosis rates may be slow, hepatocellular carcinoma and mortality rates appear to be higher among African Americans. Sustained viral response (SVR) rates have historically significantly trailed behind Caucasians. The reasons for this gap in SVR are related to both viral and host factors. Moreover, low enrollment rates in clinical trials hamper the study of the efficacy of anti-viral therapy. Nevertheless, the gap in SVR between African Americans and Caucasians may be narrowing with the use of direct-acting agents. Gastroenterologists, hepatologists, primary care physicians, and other health-care providers need to address modifiable risk factors that affect the natural history, as well as treatment outcomes, for HCV among African Americans. Efforts need to be made to improve awareness among health-care providers to address the differences in screening and referral patterns for African Americans.